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柚皮素通过降低氧化应激,减轻高血糖诱导的肝细胞核因子红细胞 2 相关因子 2 蛋白的上调。

By reducing oxidative stress, naringenin mitigates hyperglycaemia-induced upregulation of hepatic nuclear factor erythroid 2-related factor 2 protein.

机构信息

Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

出版信息

J Pharm Pharmacol. 2020 Oct;72(10):1394-1404. doi: 10.1111/jphp.13319. Epub 2020 Jul 6.

Abstract

OBJECTIVES

Antioxidant and anti-inflammatory properties of naringenin could confer hepatoprotective effects.

METHODS

Chang cells in culture media were maintained at 37°C and treated with increased concentrations of glucose (5.5-50 mm) and/or naringenin (25-100 µm), respectively, for 24 h. The cells were harvested and carbonyl proteins, antioxidant enzymes and proteins measured in cell lysates. Sprague Dawley rats were divided into 5 groups (n = 7) and orally treated daily for 56 days with 3.0 ml/kg per body weight (BW) distilled water (group 1), 60 mg/kg BW of naringenin (groups 2 and 4), respectively. Groups 3, 4 and 5 were given single 60 mg/kg per BW intraperitoneal injections of streptozotocin or insulin (2.0 IU/kg BW bid), (group 5 only).

KEY FINDINGS

Cell viability was significantly decreased in response to increased hyperglycaemia but naringenin dose-dependently, significantly reversed this compared to controls, respectively. However, antioxidant enzyme activities were reduced due to increased and reduced oxidative stress, respectively. Naringenin further significantly reduced hepatic oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression and liver : body weight ratios in diabetic compared to controls rats.

CONCLUSIONS

Naringenin confers hepatoprotective antioxidant effects by initially preventing upregulation of Nrf2 protein expression and its downstream antioxidant enzymes.

摘要

目的

柚皮素具有抗氧化和抗炎特性,可发挥肝保护作用。

方法

在 37°C 下培养的 Chang 细胞分别用不同浓度的葡萄糖(5.5-50mm)和/或柚皮素(25-100µm)处理 24 小时。收集细胞,测量细胞裂解物中的羰基蛋白、抗氧化酶和蛋白质。将 Sprague Dawley 大鼠分为 5 组(n=7),分别用 3.0ml/kg 体重(BW)蒸馏水(第 1 组)、60mg/kg BW 柚皮素(第 2 组和第 4 组)连续 56 天口服治疗。第 3 组、第 4 组和第 5 组分别单次给予 60mg/kg BW 的链脲佐菌素或胰岛素(2.0IU/kg BW bid)(仅第 5 组)腹膜内注射。

主要发现

与对照组相比,高血糖显著降低了细胞活力,但柚皮素呈剂量依赖性地显著逆转了这种情况。然而,抗氧化酶活性因氧化应激的增加和减少而降低。与对照组大鼠相比,柚皮素进一步显著降低了糖尿病大鼠的肝氧化应激和核因子红细胞 2 相关因子 2(Nrf2)蛋白表达和肝体比。

结论

柚皮素通过最初防止 Nrf2 蛋白表达及其下游抗氧化酶的上调,发挥肝保护抗氧化作用。

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